Article Summary

Aghajanian, G. K. and Bing, O. H. L. (1964). "Persistence of Lysergic Acid Diethylamide in the Plasma of Human Subjects". Clin.Pharmacol.Ther.. Vol. 5, 611-614. http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf. Retrieved 7 Dec. 2012.

Abstract
  • The concentration of a 2mcg/kg dose of LSD was measured over time in five humans. LSD was found to have a high concentration during the period of greatest effect and was found to have a half-life of 175 minutes.
Introduction
  • It is believed that LSD rapidly leaves the body and its effects are caused by secondary biochemical events.
  • This is a result of measuring only the metabolism rate of LSD in mice, which are affected for only one hour, and applying that data to humans although humans are affected for 8-12 hours.
  • Various species have greatly varied metabolic rates of LSD.
  • This study measures the plasma concentrations of LSD in humans for 8 hours following a 2mcg/kg dose.
Method
  • Five males are administered a 2mcg/kg dose of LSD via IV over 1.5min and blood samples are drawn at 5, 15, 30, 60, 120, 240, and 480 minutes following. Plasma is separated and frozen to be analyzed later.
  • All the glassware was cleaned with nonfluorescent materials and a bulk plasma sample was prepared for use with calibration by extracting it and removing fluorescent contaminants.
  • The fluorescence of the plasma was measured.
  • 0, 10, 20, and 40ng of LSD standard were added to the bulk plasma and the instrument was calibrated.
  • The method was found to be sensitive to 1ng and the standards were found to be linear with 1.5% mean deviation.
  • Subjects were given a series of equivalent 3-minute tests of addition problems both before the experiment and after each blood sample was drawn to estimate an index of performance since performance on arithmetic tests was been shown to be inversely related to LSD dose.
Results
  • During the first 30 minutes, plasma LSD levels equilibrate with tissues, resulting in a rapid decline of concentration.
  • Test scores also decrease rapidly and reach a low at 30 minutes.
  • Over time, LSD levels gradually fall and test scores gradually rise. At 8 hours, LSD levels are very low and performance is still slightly impaired.
  • The half life of LSD was calculated to be 175 min.
Discussion
  • The reported concentrations seem low, but they are actually very high for the dose administered. The 175min half life in humans in comparable to the half life in the cat and monkey and contrasts the 7min half life in mice.
  • The concentration of LSD is directly proportional to the effect produced. It is unnecessary to postulate a trigger mechanism to explain the previously-believed disappearance of LSD before effects manifest.